Efficacy of combination treatment using YHO-1701, an orally active STAT3 inhibitor, with molecular-targeted agents on cancer cell lines

Abstract Signal transducer and activator of transcription 3 (STAT3) plays a critical role in regulating cell growth, survival, and metastasis. STAT3 signaling is constitutively activated in various types of hematologic or solid malignancies. YHO-1701 has been developed as an orally available STAT3 i...

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Autores principales:	Keisuke Taniguchi, Hiroaki Konishi, Akiko Yoshinaga, Momomi Tsugane, Hiroyuki Takahashi, Fukiko Nishisaka, Yoshiyuki Shishido, Akira Asai
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b2fd71e3e98c45489e828ff9edfd8062
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spelling	oai:doaj.org-article:b2fd71e3e98c45489e828ff9edfd80622021-12-02T16:36:12ZEfficacy of combination treatment using YHO-1701, an orally active STAT3 inhibitor, with molecular-targeted agents on cancer cell lines10.1038/s41598-021-86021-82045-2322https://doaj.org/article/b2fd71e3e98c45489e828ff9edfd80622021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86021-8https://doaj.org/toc/2045-2322Abstract Signal transducer and activator of transcription 3 (STAT3) plays a critical role in regulating cell growth, survival, and metastasis. STAT3 signaling is constitutively activated in various types of hematologic or solid malignancies. YHO-1701 has been developed as an orally available STAT3 inhibitor. Herein, YHO-1701 in combination with molecular-targeted agents was evaluated. Additive or synergistic effects were observed in a broad spectrum of “combination treatment + cell line” pairs. Of particular interest was the synergistic effect observed when YHO-1701 was combined with imatinib or dasatinib [breakpoint cluster region-abelson (BCR-ABL) inhibitors], osimertinib [epidermal growth factor receptor (EGFR) inhibitor], crizotinib, alectinib, or ceritinib [anaplastic lymphoma kinase (ALK) inhibitors]. The results further showed a close relationship between these synergistic effects and the cellular levels of the key molecules involved in the target pathways for YHO-1701 and each combination drug. The combination of YHO-1701 with alectinib resulted in significantly greater antitumor activity without exhibiting body weight loss in an NCI-H2228 [echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion] xenograft mouse model. Our results strongly suggest that the logical strategy in combination with the novel STAT3 inhibitor YHO-1701 and other mechanistically different targeted agents, could be a promising approach in future clinical settings.Keisuke TaniguchiHiroaki KonishiAkiko YoshinagaMomomi TsuganeHiroyuki TakahashiFukiko NishisakaYoshiyuki ShishidoAkira AsaiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Keisuke Taniguchi Hiroaki Konishi Akiko Yoshinaga Momomi Tsugane Hiroyuki Takahashi Fukiko Nishisaka Yoshiyuki Shishido Akira Asai Efficacy of combination treatment using YHO-1701, an orally active STAT3 inhibitor, with molecular-targeted agents on cancer cell lines
description	Abstract Signal transducer and activator of transcription 3 (STAT3) plays a critical role in regulating cell growth, survival, and metastasis. STAT3 signaling is constitutively activated in various types of hematologic or solid malignancies. YHO-1701 has been developed as an orally available STAT3 inhibitor. Herein, YHO-1701 in combination with molecular-targeted agents was evaluated. Additive or synergistic effects were observed in a broad spectrum of “combination treatment + cell line” pairs. Of particular interest was the synergistic effect observed when YHO-1701 was combined with imatinib or dasatinib [breakpoint cluster region-abelson (BCR-ABL) inhibitors], osimertinib [epidermal growth factor receptor (EGFR) inhibitor], crizotinib, alectinib, or ceritinib [anaplastic lymphoma kinase (ALK) inhibitors]. The results further showed a close relationship between these synergistic effects and the cellular levels of the key molecules involved in the target pathways for YHO-1701 and each combination drug. The combination of YHO-1701 with alectinib resulted in significantly greater antitumor activity without exhibiting body weight loss in an NCI-H2228 [echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion] xenograft mouse model. Our results strongly suggest that the logical strategy in combination with the novel STAT3 inhibitor YHO-1701 and other mechanistically different targeted agents, could be a promising approach in future clinical settings.
format	article
author	Keisuke Taniguchi Hiroaki Konishi Akiko Yoshinaga Momomi Tsugane Hiroyuki Takahashi Fukiko Nishisaka Yoshiyuki Shishido Akira Asai
author_facet	Keisuke Taniguchi Hiroaki Konishi Akiko Yoshinaga Momomi Tsugane Hiroyuki Takahashi Fukiko Nishisaka Yoshiyuki Shishido Akira Asai
author_sort	Keisuke Taniguchi
title	Efficacy of combination treatment using YHO-1701, an orally active STAT3 inhibitor, with molecular-targeted agents on cancer cell lines
title_short	Efficacy of combination treatment using YHO-1701, an orally active STAT3 inhibitor, with molecular-targeted agents on cancer cell lines
title_full	Efficacy of combination treatment using YHO-1701, an orally active STAT3 inhibitor, with molecular-targeted agents on cancer cell lines
title_fullStr	Efficacy of combination treatment using YHO-1701, an orally active STAT3 inhibitor, with molecular-targeted agents on cancer cell lines
title_full_unstemmed	Efficacy of combination treatment using YHO-1701, an orally active STAT3 inhibitor, with molecular-targeted agents on cancer cell lines
title_sort	efficacy of combination treatment using yho-1701, an orally active stat3 inhibitor, with molecular-targeted agents on cancer cell lines
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/b2fd71e3e98c45489e828ff9edfd8062
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Efficacy of combination treatment using YHO-1701, an orally active STAT3 inhibitor, with molecular-targeted agents on cancer cell lines

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